Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decitabine (DAC) and 5-azacitidine have recently been approved for the treatment of myelodysplastic syndrome. The pharmacodynamic effects of DAC and 5-azacitidine outside their known activity as inhibitors of DNA methyltransferases (DNMTs) require further investigation. The purpose of this study was to investigate the effect of DAC on the expression of p21(WAF1/CIP1), a gene with a putative CpG island surrounding its promoter region. Promoter methylation analysis of p21(WAF1/CIP1) in leukemia cells revealed the absence of CpG methylation. However, DAC upregulated p21(WAF1/CIP1) expression in a dose-dependent manner (ED(50)=103.34 nM) and induced G2/M cell cycle arrest in leukemia cells. Sequential application of DAC followed by different histone deacetylase inhibitors induced expression of p21(WAF1/CIP1) synergistically. Upregulation of p21(WAF1/CIP1) paralleled DAC-induced apoptosis (ED(50)=153 nM). Low doses of DAC induced gamma-H2AX expression (ED(50)=16.5 nM) and upregulated p21(WAF1/CIP1) in congenic HCT 116 colon cancer cells in a DNMT-independent and p53-dependent fashion. Inhibition of p53 transactivation by pifithrin-alpha or the kinase activity of ATM by either the specific ATM inhibitor KU-5593 or caffeine abrogated p21(WAF1/CIP1) upregulation, indicating that DAC upregulation of p21(WAF1/CIP1) was p53- and ATM-dependent in leukemia cells. In conclusion, DAC upregulates p21(WAF1/CIP1) in DNMT-independent manner via the DNA damage/ATM/p53 axis.
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PMID:p21(WAF1/CIP1) induction by 5-azacytosine nucleosides requires DNA damage. 1822 91

To investigate the effect of multi-disciplinary teamwork on balance performance of Parkinson's disease (PD).Sixteen primary Parkinson's disease patients (8 male, 8 female) treated with bilateral subthalamic nucleus deep brain stimulation (STN-DBS) were included in the study. The median age of patients was 60.5 years; all patients were in the Hoehn&Yahr (H&Y) 3 stage; the median PD duration of the disease was 9 years. For each patient, multi-disciplinary teamwork treatment including DBS, medication, physical therapy and psychotherapy proceeded. levodopa equivalent daily dose (LEDD, mg/day), life quality (PDQ-39), Motor disability (MDS-UPDRSIII) and balance performance (MDS-UPDRS 3.12, Berg Balance Scale BBS, Limits of Stability LoS) were assessed in different time and status respectively: preoperation (Med-off, Med-on), postoperation (Stim-Off/Med-Off, Stim-On/Med-Off, Stim-On/Med-On), 6 months postoperation (Stim-On/ Med-Off, Stim-On/Med-On) and 12 months postoperation (Stim-On/Med-Off, Stim-On/Med-On).The LEDD, life quality (PDQ-39) continued to improve during the follow-up, statistical difference were found in both 6 months postoperation and 12 months postoperation compared with preoperation. The Motor disability (MDS-UPDRSIII), balance performance (MDS-UPDRS 3.12, BBS) and the LoS (target acquisition percentage, trunk swing angle standard deviation, time) showed significant improvement in Stim-On/med-Off 6 months postoperation and 12 months postoperation separately compared with Med-Off preoperation.Multi-disciplinary teamwork for PD patients with STN-DBS could improve balance performance.
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PMID:Clinical experience of comprehensive treatment on the balance function of Parkinson's disease. 3238 3